| Project/Area Number |
17K09846
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | β細胞 / Pbk / Ccnb1 / Estradiol / p53 / 糖尿病 / 妊娠 / インスリン / 細胞増殖 / エストラジオール / サイクリンB１ / 膵島 |
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| Outline of Final Research Achievements |
The proliferation of pancreatic β-cells is enhanced to enable an increase in β-cell mass during pregnancy. To elucidate the mechanisms involved, we investigated islets from pregnant and nonpregnant mice by gene expression profiling, and found that the expression of Pbk is increased in pregnant mouse islets compared with control mouse islets. Among the pregnancy hormones, treatment with estradiol upregulated Pbk expression. Knockdown of Pbk reduced BrdU incorporation in MIN6 cells, which was accompanied with a decreased expression of Ccnb1, a regulatory gene involved in mitosis. Ccnb1 expression was augmented in mouse islets during pregnancy. The forced expression of Pbk in isolated mouse islets increased Ccnb1 expression, and the Pbk inhibitor HI-TOPK-032 suppressed Ccnb1 expression in islets isolated from pregnant mice. Our results suggest that Pbk contributes to the expansion of islets during pregnancy, and Ccnb1 may assist Pbk in its role in β-cell proliferation.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病は1型糖尿病あるいは2型糖尿病に限らず、その発症にはβ細胞量の低下が関与している。現在、β細胞を補充する治療として、臨床現場で提供されている唯一の方法が膵/膵島移植であるが、ドナー不足により適応が極めて限定される。本研究は、妊娠期にβ細胞が増加することに着目し、その新規メカニズムの一端を明らかにしている。患者自身のβ細胞を十分に増やすことができれば、血糖値の改善や正常化が可能となる。本研究は、β細胞の増殖を標的とする新たな糖尿病治療法開発の一助となることが期待される。
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